Journal of Biomolecular Structure & Dynamics最新文献

{"title":"Phytochemical composition, anti-microbial, anti-oxidant and anti-diabetic effects of <i>Solanum elaeagnifolium</i> Cav. leaves: <i>in vitro</i> and <i>in silico</i> assessments.","authors":"Francis Xavier T, Sabitha R, Freeda Rose A K, Balavivekananthan S, Kariyat R, Ayyanar M, Vijayakumar S, Prabhu S, Amalraj S, Shine K, Thiruvengadam M","doi":"10.1080/07391102.2023.2300124","DOIUrl":"10.1080/07391102.2023.2300124","url":null,"abstract":"<p><p>The aim of this study was to screen the chemical components of <i>Solanum elaeagnifolium</i> leaves and assess their therapeutic attributes with regard to their antioxidant, antibacterial, and antidiabetic activities. The antidiabetic effects were explored to determine the α-amylase and α-glucosidase inhibitory potential of the leaf extract. To identify the active antidiabetic drugs from the extracts, the GC-MS-screened molecules were docked with diabetes-related proteins using the glide module in the Schrodinger Tool. In addition, molecular dynamics (MD) simulations were performed for 100 ns to evaluate the binding stability of the docked complex using the Desmond module. The ethyl acetate had a significant total phenolic content (TPC), with a value of 79.04 ± 0.98 mg/g GAE. The ethanol extract was tested for its minimum inhibitory concentration (MIC) for its bacteriostatic properties. It suppressed the growth of <i>B. subtilis, E. coli, P. vulgaris, R. equi</i> and <i>S. epidermis</i> at a dosage of 118.75 µg/mL. Moreover, the IC50 values of the ethanol extract were determined to be 17.78 ± 2.38 in the α-amylase and and 27.90 ± 5.02 µg/mL in α-glucosidase. The <i>in-silico</i> investigation revealed that cyclolaudenol achieved docking scores of -7.94 kcal/mol for α-amylase. Likewise, the α-tocopherol achieved the docking scores of -7.41 kcal/mol for glycogen phosphorylase B and -7.21 kcal/mol for phosphorylase kinase. In the MD simulations, the cyclolaudenol and α-tocopherol complexes exhibited consistently stable affinities with diabetic proteins throughout the trajectory. Based on these findings, we conclude that this plant could be a good source for the development of novel antioxidant, antibacterial, and antidiabetic agents.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"3688-3714"},"PeriodicalIF":2.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139097855","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biochemical and molecular docking-based strategies of <i>Acalypha indica</i> and <i>Boerhavia diffusa</i> extract by targeting bacterial strains and cancer proteins.","authors":"Mst Sharmin Sultana Shimu, Gobindo Kumar Paul, Amit Kumar Dutta, Changhyun Kim, Md Abu Saleh, Md Asadul Islam, Uzzal Kumar Acharjee, Bonglee Kim","doi":"10.1080/07391102.2023.2297011","DOIUrl":"10.1080/07391102.2023.2297011","url":null,"abstract":"<p><p>Antibiotic-resistant microbes have emerged around the world, presenting a risk to health. Plant-derived drugs have become a potential source for the production of antibiotic-resistant drugs and cancer therapies. In this study, we investigated the antibacterial, cytotoxic and antioxidant properties of <i>Acalypha indica</i> and <i>Boerhavia diffusa</i>, and conducted <i>in silico</i> molecular docking experiments against EGFR and VEGFR-2 proteins. The metabolic extract of <i>A. indica</i> inhibited <i>Streptococcus iniae</i> and <i>Staphylococcus sciuri</i> with inhibition zones of 21.66 ± 0.57 mm and 20.33 ± 0.57 mm, respectively. The <i>B. diffusa</i> leaf extract produced inhibition zones of 20.3333 ± 0.5773 mm and 20.33 ± 0.57 mm against <i>Streptococcus iniae</i> and <i>Edwardsiella anguillarum</i>, respectively. <i>A. indica</i> and <i>B. diffusa</i> extracts had toxicities of 162.01 μg/ml and 175.6 μg/ml, respectively. Moreover, <i>B. diffusa</i> (IC₅₀ =154.42 µg/ml) leaf extract exhibited moderately higher antioxidant activity compared with the <i>A. indica</i> (IC₅₀ = 218.97 µg/ml) leaf extract. Multiple interactions were observed at Leu694, Met769 and Leu820 sites for EGFR and at Asp1046 and Cys1045 sites for VEGFR during the molecular docking study. CID-235030, CID-70825 and CID-156619353 had binding energies of -7.6 kJ/mol, -7.5 kJ/mol and -7.6 kJ/mol, respectively, with EGFR protein. VEGFR-2 protein had docking energies of -7.5 kJ/mol, -7.6 kJ/mol and -7.3 kJ/mol, respectively, for CID-6420353, CID-156619353 and CID-70825 compounds. The MD simulation trajectories revealed the hit compound; CID-235030 and EGFR complex, CID-6420353 and VEGFR-2 exhibit stable profile in the root mean square deviation (RMSD), radius of gyration (Rg), solvent accessible surface area (SASA), hydrogen bond and root mean square fluctuation (RMSF) and the binding free energy by MM-PBSA method. This study indicates that methanol extracts of <i>A. indica</i> and <i>B. diffusa</i> may play a crucial role in developing antibiotic-resistant and cancer drugs.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"3330-3347"},"PeriodicalIF":2.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139037740","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comprehensive amino acid composition analysis of seed storage proteins of cereals and legumes: identification and understanding of intrinsically disordered and allergenic peptides.","authors":"Pratibha Sharma, Lakshay Malhotra, Rajinder K Dhamija","doi":"10.1080/07391102.2023.2300126","DOIUrl":"10.1080/07391102.2023.2300126","url":null,"abstract":"<p><p>The seed storage proteins of cereal and legumes are the primary source of amino acids which are required for sustaining the nitrogen and carbon demands during germination and growth. Humans derive most of their dietary proteins from storage proteins in form of a wide variety of foods, for consumption. The amino acid content of most of these proteins is biased and the need for this biasness is not understood. The high abundance of proline, glutamine, and cysteine in cereals makes the gluten fraction viscoelastic. The cereal proteins have less charge and legume proteins have more charge on them. Their non-polar amino acid distribution has large variations. These characteristics are strongly responsible for the partial and complete unfolding of several domains of the storage proteins. Many of the storage proteins share a highly conserved structural feature within the cupin superfamily spread across all kingdoms of life. The intrinsically disordered viscoelastic proteins help in making dough which is vital for the quality of bread. Unfolded regions harbor more immunogenic sequences and cause food-related allergies and intolerance. We have discussed these properties in terms of comparison of cereal and legume storage protein sequences and allergy. Our study supports the findings that large disordered regions contain allergen-representative peptides. Interestingly, a high number of allergen-representative peptides were cleavable by digestive enzymes. Furthermore, unfolded storage proteins mimic microbial immunogens to induce a memory immune response. Results findings can be used to guide the understanding of immunological characteristics of storage proteins and may assist in treatment decisions for food allergy.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"3715-3727"},"PeriodicalIF":2.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139097853","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of potential inhibitors against <i>Escherichia coli</i> Mur D enzyme to combat rising drug resistance: an <i>in-silico</i> approach.","authors":"Vinita Gaur, Neeraj Kumar, Ashish Vyas, Debabrata Chowdhury, Joginder Singh, Surojit Bera","doi":"10.1080/07391102.2023.2297007","DOIUrl":"10.1080/07391102.2023.2297007","url":null,"abstract":"<p><p>Indiscriminate use of anti-microbial agents has resulted in the inception, frequency, and spread of antibiotic resistance among targeted bacterial pathogens and the commensal flora. Mur enzymes, playing a crucial role in cell-wall synthesis, are one of the most appropriate targets for developing novel inhibitors against antibiotic-resistant bacterial pathogens. In the present study, <i>in-silico</i> high-throughput virtual (HTVS) and Standard-Precision (SP) screening was carried out with 0.3 million compounds from several small-molecule libraries against the <i>E. coli</i> Mur D enzyme (PDB ID 2UUP). The docked complexes were further subjected to extra-precision (XP) docking calculations, and highest Glide-score compound was further subjected to molecular simulation studies. The top six virtual hits (S1-S6) displayed a glide score (G-score) within the range of -9.013 to -7.126 kcal/mol and compound S1 was found to have the highest stable interactions with the Mur D enzyme (2UUP) of E. <i>coli</i>. The stability of compound S1 with the Mur D (2UUP) complex was validated by a 100-ns molecular dynamics simulation. Binding free energy calculation by the MM-GBSA strategy of the S1-2UUP (Mur D) complex established van der Waals, hydrogen bonding, lipophilic, and Coulomb energy terms as significant favorable contributors for ligand binding. The final lead molecules were subjected to ADMET predictions to study their pharmacokinetic properties and displayed promising results, except for certain modifications required to improve QPlogHERG values. So, the compounds screened against the Mur D enzyme can be further studied as preparatory points for <i>in-vivo</i> studies to develop potential drugs. HIGHLIGHTS<i>E.coli</i> is a common cause of urinary tract infections.<i>E.coli</i> MurD enzyme is a suitable target for drug development.Novel inhibitors against <i>E.coli</i> MurD enzyme were identified.Molecular dynamics studies identified <i>in-silico</i> potential of identified compound.ADMET predictions and Lipinski's rule of five studies showed promising results.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"3286-3296"},"PeriodicalIF":2.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139040040","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigating the bispecific lead compounds against methicillin-resistant <i>Staphylococcus aureus</i> SarA and CrtM using machine learning and molecular dynamics approach.","authors":"Kareem M Younes, Amr S Abouzied, Ahmed Alafnan, Bader Huwaimel, Weam M A Khojali, Rami M Alzahrani","doi":"10.1080/07391102.2023.2297012","DOIUrl":"10.1080/07391102.2023.2297012","url":null,"abstract":"<p><p>Methicillin-resistant Staphylococcus aureus (MRSA) is a notorious pathogen that has emerged as a serious global health concern over the past few decades. Staphylococcal accessory regulator A (SarA) and 4,4'-diapophytoene synthase (CrtM) play a crucial role in biofilm formation and staphyloxanthin biosynthesis. Thus, the present study used a machine learning-based QSAR model to screen 1261 plant-derived natural organic compounds in order to identify a medication candidate with both biofilm and virulence inhibitory potential. Additionally, the <i>in-silico</i> molecular docking analysis has demonstrated significant binding efficacy of the identified hit compound, that is 85137543, with SarA and CrtM when compared to the control compound, hesperidin. Post-MD simulation analysis of the complexes depicted strong binding of <b>85137543</b> to both SarA and CrtM. Moreover, <b>85137543</b> showed hydrogen bonding with the key residues of both proteins during docking (ALA138 of SarA and ALA134 of CrtM) and post-MD simulation (LYS273 of CrtM and ASN212 of SarA). The RMSD of <b>85137543</b> was stable and consistent when bound to both CrtM and SarA with RMSDs of 1.3 and 1 nm, respectively. In addition, principal component analysis and the free energy landscape showed stable complex formation with both proteins. Low binding free energy (ΔGTotal) was observed by <b>85137543</b> for SarA (-47.92 kcal/mol) and CrtM (-36.43 kcal/mol), which showed strong binding. Overall, this study identified <b>85137543</b> as a potential inhibitor of both SarA and CrtM in MRSA.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"3348-3365"},"PeriodicalIF":2.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139040042","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Features of the rare pathogen <i>Meyerozyma guilliermondii</i> strain SO and comprehensive <i>in silico</i> analyses of its adherence-contributing virulence factor agglutinin-like sequences.","authors":"Si Jie Lim, Noor Dina Muhd Noor, Suriana Sabri, Mohd Shukuri Mohamad Ali, Abu Bakar Salleh, Siti Nurbaya Oslan","doi":"10.1080/07391102.2023.2300757","DOIUrl":"10.1080/07391102.2023.2300757","url":null,"abstract":"<p><p><i>Meyerozyma guilliermondii</i> is a rare yeast pathogen contributing to the deadly invasive candidiasis. <i>M. guilliermondii</i> strain SO, as a promising protein expression host, showed 99% proteome similarity with the clinically isolated ATCC 6260 (type strain) in a recent comparative genomic analysis. However, their <i>in vitro</i> virulence features and <i>in vivo</i> pathogenicity were uncharacterized. This study aimed to characterize the <i>in vitro</i> and <i>in vivo</i> pathogenicity of <i>M. guilliermondii</i> strain SO and analyze its Als proteins (<i>Mg</i>Als) <i>via</i> comprehensive bioinformatics approaches. <i>M. guilliermondii</i> strain SO showed lower and higher sensitivity towards β-mercaptoethanol and lithium, respectively than the avirulent <i>S. cerevisiae</i> but exhibited the same tolerance towards cell wall-perturbing Congo Red with <i>C. albicans</i>. With 7.5× higher biofilm mass, <i>M. guilliermondii</i> strain SO also demonstrated 75% higher mortality rate in the zebrafish embryos with a thicker biofilm layer on the chorion compared to the avirulent <i>S. cerevisiae</i>. Being one of the most important <i>Candida</i> adhesins, sequence and structural analyses of four statistically identified <i>Mg</i>Als showed that <i>Mg</i>Als1056 was predicted to exhibit the most conserved amyloid-forming regions, tandem repeat domain and peptide binding cavity (PBC) compared to <i>C. albicans</i> Als3. Favoured from the predicted largest ligand binding site and druggable pockets, it showed the highest affinity towards hepta-threonine. Non-PBC druggable pockets in the most potent virulence contributing <i>Mg</i>Als1056 provide new insights into developing antifungal drugs targeting non-<i>albicans Candida</i> spp. Virtual screening of available synthetic or natural bioactive compounds and <i>Mg</i>Als1056 deletion from the fungal genome should be further performed and validated experimentally.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"3728-3748"},"PeriodicalIF":2.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139377685","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Understanding a point mutation signature D54K in the caspase activation recruitment domain of NOD1 capitulating concerted immunity via atomistic simulation.","authors":"P Raghuraman, Sriroopreddy Ramireddy, Gurusamy Raman, SeonJoo Park, C Sudandiradoss","doi":"10.1080/07391102.2024.2322618","DOIUrl":"10.1080/07391102.2024.2322618","url":null,"abstract":"<p><p>Point mutation D54K in the human N-terminal caspase recruitment domain (CARD) of nucleotide-binding oligomerization domain -1 (NOD1) abrogates an imperative downstream interaction with receptor-interacting protein kinase (RIPK2) that entails combating bacterial infections and inflammatory dysfunction. Here, we addressed the molecular details concerning conformational changes and interaction patterns (monomeric-dimeric states) of D54K by signature-based molecular dynamics simulation. Initially, the sequence analysis prioritized D54K as a pathogenic mutation, among other variants, based on a sequence signature. Since the mutation is highly conserved, we derived the distant ortholog to predict the sequence and structural similarity between native and mutant. This analysis showed the utility of 33 communal core residues associated with structural-functional preservation and variations, concurrently served to infer the cryptic hotspots Cys39, Glu53, Asp54, Glu56, Ile57, Leu74, and Lys78 determining the inter helical fold forming homodimers for putative receptor interaction. Subsequently, the atomistic simulations with free energy (MM/PB(GB)SA) calculations predicted structural alteration that takes place in the N-terminal mutant CARD where coils changed to helices (45 _{α3- L4-α4-L6- α6}83) in contrast to native (45_{T2-L4-α4-L6-T4}83). Likewise, the C-terminal helices 93_T1-α7105 connected to the loops distorted compared to native 93_α6-L7105 may result in conformational misfolding that promotes functional regulation and activation. These structural perturbations of D54K possibly destabilize the flexible adaptation of critical homotypic _NOD1CARD-CARD_RIPK2 interactions (_α4Asp42-Arg488_α5 and _α6Phe86-Lys471_α4) is consistent with earlier experimental reports. Altogether, our findings unveil the conformational plasticity of mutation-dependent immunomodulatory response and may aid in functional validation exploring clinical investigation on CARD-regulated immunotherapies to prevent systemic infection and inflammation.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"3766-3782"},"PeriodicalIF":2.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139983009","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular insights to the anti-COVID-19 potential of α-, β- and γ-cyclodextrins.","authors":"Vipul Kumar, Hazna Noor Meidinna, Sunil C Kaul, Dharmender Gupta, Yoshiyuki Ishida, Keiji Terao, Sudhanshu Vrati, Durai Sundar, Renu Wadhwa","doi":"10.1080/07391102.2023.2294385","DOIUrl":"10.1080/07391102.2023.2294385","url":null,"abstract":"<p><p>SARS-CoV-2 viral infection is regulated by the host cell receptors ACE2 and TMPRSS2, and therefore the effect of various natural and synthetic compounds on these receptors has recently been the subject of investigations. Cyclodextrins, naturally occurring polysaccharides derived from starch, are soluble in water and have a hydrophobic cavity at their center enabling them to accommodate small molecules and utilize them as carriers in the food, supplements, and pharmaceutical industries to improve the solubility, stability, and bioavailability of target compounds. In the current study, computational molecular simulations were used to investigate the ability of α-, β- and γ-Cyclodextrins on human cell surface receptors. Cell-based experimental approaches, including expression analyses at mRNA and protein levels and virus replication, were used to assess the effect on receptor expression and virus infection, respectively. We found that none of the three CDs could dock effectively to human cell surface receptor ACE2 and viral protease M^pro (essential for virus replication). On the other hand, α- and β-CD showed strong and stable interactions with TMPRSS2, and the expression of both ACE2 and TMPRSS2 was downregulated at the mRNA and protein levels in cyclodextrin (CD)-treated cells. A cell-based virus replication assay showed ∼20% inhibition by β- and γ-CD. Taken together, the study suggested that (i) downregulation of expression of host cell receptors may not be sufficient to inhibit virus infection (ii) activity of the receptors and virus protein M^pro may play a critical and clinically relevant role, and hence (iii) newly emerging anti-Covid-19 compounds warrant multimodal functional analyses.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"2890-2900"},"PeriodicalIF":2.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138803986","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular dynamics, molecular docking, DFT, and ADMET investigations of the Co(II), Cu(II), and Zn(II) chelating on the antioxidant activity and SARS-CoV-2 main protease inhibition of quercetin.","authors":"El Hassane Anouar","doi":"10.1080/07391102.2023.2294372","DOIUrl":"10.1080/07391102.2023.2294372","url":null,"abstract":"<p><p>The natural flavonol quercetin (Q) is found in many vegetables, fruits, and beverages, and it is known as a strong antioxidant. Its metal ion chelation may increase its antioxidant activity. The present study aims to explore the Co(II), Cu(II), and Zn(II) chelating on the antioxidant effectiveness and severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) main protease (M^pro) inhibitory of quercetin using Density-functional theory (DFT), molecular docking, and molecular dynamics simulations (MD). DFT calculations at the B3LYP/LanL2DZ reveal that the high antioxidant activity of the metal-chelated quercetin complexes is mainly returned to their lower ionization potentials (IPs) compared with the one of the free quercetin. Molecular docking of quercetin and its Co(II), Cu(II), and Zn(II) chelates into the active binding sites of peroxiredoxin 5 and SARS-CoV-2 main protease (M^pro) were performed using Lamarckian Genetic Algorithm method. The docked quercetin and its metal chelates fit well into the binding site of the target proteins, and their binding affinity is strongly influenced by the type of the chelated metals Co(II), Cu(II), and Zn(II), and molar ratio metal: ligand, i.e. 1:2 and 2:1. Further, the binding stability of QZn₂ and QCu₂ in peroxiredoxin 5 and SARS-CoV-2 main protease targets is evaluated using MD simulation conducted for 100 ns simulations at natural room temperature conditions, and the obtained results showed that all chelates remain bound to the ligand binding groove of protein except for 1HD2_QZn₂ complex. Finally, the adsorption, distribution, metabolism, excretion, and toxicity (ADMET) and drug-likeness properties of quercetin and cobalt(II)-quercetin (QCo₂(II)) were investigated.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"2719-2732"},"PeriodicalIF":2.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138803883","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Screening of phytochemicals from <i>Clerodendrum inerme</i> (L.) Gaertn as potential anti-breast cancer compounds targeting EGFR: an <i>in-silico</i> approach.","authors":"Nusrath Yasmeen, Anis Ahmad Chaudhary, Ravi Ranjan K Niraj, Sudarshan S Lakhawat, Pushpender K Sharma, Vikram Kumar","doi":"10.1080/07391102.2023.2294379","DOIUrl":"10.1080/07391102.2023.2294379","url":null,"abstract":"<p><p>Breast cancer (BC) is the most prevalent malignancy among women around the world. The epidermal growth factor receptor (EGFR) is a tyrosine kinase receptor (RTK) of the ErbB/HER family. It is essential for triggering the cellular signaling cascades that control cell growth and survival. However, perturbations in EGFR signaling lead to cancer development and progression. Hence, EGFR is regarded as a prominent therapeutic target for breast cancer. Therefore, in the current investigation, EGFR was targeted with phytochemicals from <i>Clerodendrum inerme</i> (L.) Gaertn (<i>C. inerme</i>). A total of 121 phytochemicals identified by gas chromatography-mass spectrometry (GC-MS) analysis were screened against EGFR through molecular docking, ADMET analyses (Absorption, Distribution, Metabolism, Excretion, and Toxicity), PASS predictions, and molecular dynamics simulation, which revealed three potential hit compounds with CIDs 10586 [i.e. alpha-bisabolol (-6.4 kcal/mol)], 550281 [i.e. 2,(4,4-Trimethyl-3-hydroxymethyl-5a-(3-methyl-but-2-enyl)-cyclohexene) (-6.5 kcal/mol)], and 161271 [i.e. salvigenin (-7.4 kcal/mol)]. The <i>FDA-</i>approved drug gefitinib was used to compare the inhibitory effects of the phytochemicals. The top selected compounds exhibited good ADMET properties and obeyed Lipinski's rule of five (ROF). The molecular docking analysis showed that salvigenin was the best among the three compounds and formed bonds with the key residue Met 793. Furthermore, the molecular mechanics generalized born surface area (MMGBSA) calculations, molecular dynamics simulation, and normal mode analysis validated the binding affinity of the compounds and also revealed the strong stability and compactness of phytochemicals at the docked site. Additionally, DFT and DOS analyses were done to study the reactivity of the compounds and to further validate the selected phytochemicals. These results suggest that the identified phytochemicals possess high inhibitory potential against the target EGFR and can treat breast cancer. However, further <i>in vitro</i> and <i>in vivo</i> investigations are warranted towards the development of these constituents into novel anti-cancer drugs.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":" ","pages":"2781-2823"},"PeriodicalIF":2.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139032357","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}